Department of Neurology, Affiliated Hospital, Guangdong Medical College, Zhanjiang, China.
Pharmacol Rep. 2011;63(2):381-91. doi: 10.1016/s1734-1140(11)70504-7.
Activation of the NF-κB pathway plays an important role in the pathophysiology of Alzheimer's disease (AD), and blocking NF-κB pathway activation has been shown to attenuate cognitive impairment. Diabetic metabolic disorder contributes to β-amyloid protein (Aβ) generation. The goal of this study was to determine the effect of minocycline on Aβ generation and the NF-κB pathway in the hippocampus of diabetic rats and to elucidate the neuroprotective mechanisms of minocycline for the treatment of diabetic metabolic disorder. The diabetic rat model was established using a high-fat diet and an intraperitoneal injection of streptozocin (STZ). Behavioral tests showed that the capacity of learning and memory was significantly lower in diabetic rats. The levels of NF-κB, COX-2, iNOS, IL-1β and TNF-α after the STZ injection were significantly increased in the hippocampus. Significant increases in Aβ, BACE1, NF-κB, COX-2, iNOS, IL-1β and TNF-α were found in diabetic rats. The levels of Aβ, NF-κB, COX-2, iNOS, IL-1β and TNF-α were significantly decreased after minocycline administration; however, minocycline had no effect on BACE1 expression. In sum, diabetes contributes to the activation of the NF-κB pathway and upregulates BACE1 and Aβ. Minocycline downregulates Aβ in the hippocampus by inhibiting NF-κB pathway activation.
NF-κB 通路的激活在阿尔茨海默病（AD）的病理生理学中起着重要作用，阻断 NF-κB 通路的激活已被证明可以减轻认知障碍。糖尿病代谢紊乱导致β-淀粉样蛋白（Aβ）生成。本研究的目的是确定米诺环素对糖尿病大鼠海马中 Aβ生成和 NF-κB 通路的影响，并阐明米诺环素治疗糖尿病代谢紊乱的神经保护机制。使用高脂肪饮食和链脲佐菌素（STZ）腹腔注射建立糖尿病大鼠模型。行为测试表明，糖尿病大鼠的学习和记忆能力明显降低。STZ 注射后，海马中 NF-κB、COX-2、iNOS、IL-1β 和 TNF-α 的水平明显升高。糖尿病大鼠中 Aβ、BACE1、NF-κB、COX-2、iNOS、IL-1β 和 TNF-α 的水平显著升高。米诺环素给药后 Aβ、NF-κB、COX-2、iNOS、IL-1β 和 TNF-α 的水平显著降低；然而，米诺环素对 BACE1 表达没有影响。总之，糖尿病导致 NF-κB 通路的激活，并上调 BACE1 和 Aβ。米诺环素通过抑制 NF-κB 通路的激活来下调海马中的 Aβ。
